Bioavailability Enhancement: When to Use Hot-Melt Extrusion versus Spray Drying

Enhancing bioavailability can be achieved through hot-melt extrusion (HME) or spray drying. The drug product's API properties and stage of development are important factors to consider when deciding which technique to use. There are also considerations to be made with regard to process, time and cost. To gain perspective on these issues as well as insight into more recent advances in HME and spray drying, Pharmaceutical Technology Europe (PTE) spoke to Bend Research, an independent drug-formulation developm

PTE: One tool for bioavailability enhancement is to create amorphous solid dispersions through processes such as hot-melt extrusion (HME) or spray drying. What factors come into play to decide whether to produce the amorphous solid dispersions through HME or spray drying?

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Bend Research: Both spray drying and HME can be used to produce amorphous dispersions that enhance the bioavailability of poorly soluble compounds. There are a number of factors that come into play when deciding to progress an amorphous dispersion. These include performance, projected dose, stability and manufacturability. When choosing which technology to employ for optimising the amorphous dispersion formulation's performance, two key factors are the physical-chemical properties of the API and the phase of development, which influences the amount of API available for formulation development.

Important physical–chemical properties include the solubility of the API in either a solvent (for spray drying) or polymer (for HME), the melting temperature of the API and the LogP value of the API. For spray drying, the solubility of the API in the solvent is crucial to ensure a readily scalable and viable process, whereas for HME, the solubility of the API in the polymer is crucial to ensure a thermodynamically stable system. The particle size of the API, which influences the dissolution rate during processing, can also be crucial for complete dissolution into the polymer melt.

The processing temperature is important for HME because the API must either melt to form a dispersion or dissolve through high shear forces into the molten polymer. If the processing temperature is too high, the compound or the polymer used in the formulation can degrade. Typically, 200 °C to 225 °C is regarded as the upper processing-temperature limit for an effective HME process. Although compounds can be extruded at higher processing temperatures, this physical situation often produces a partially crystalline formulation instead of an amorphous dispersion.

The phase of development is also an important factor in process selection. For example, for early-stage or discovery-support activities, API availability is often limited. This limited API availability tends to make spray drying the preferable process because its feasibility can be determined with as little as 50 to 100 mg of API, whereas several grams of API are typically required to develop an initial HME process. For APIs that are amenable to HME, typically after proof-of-concept clinical studies, when hundreds of grams of API are available, an initial spray-drying process can be converted from spray drying to HME.